Inhibition of EZH2 degradation as a novel approach to overcome drug resistance in acute myeloid leukemia

Stefanie Göllner; Carsten Müller-Tidow

doi:10.1080/23723556.2017.1291396

Inhibition of EZH2 degradation as a novel approach to overcome drug resistance in acute myeloid leukemia

Mol Cell Oncol. 2017 Feb 15;4(2):e1291396. doi: 10.1080/23723556.2017.1291396. eCollection 2017.

Authors

Stefanie Göllner¹, Carsten Müller-Tidow¹

Affiliation

¹ Department of Medicine IV, Hematology and Oncology, University Hospital of Halle (Saale), Halle (Saale), Germany; Department of Internal Medicine V, Hematology, Oncology and Rheumatology, University Hospital of Heidelberg, Heidelberg, Germany.

Abstract

The polycomb protein enhancer of zeste homolog 2 (EZH2) may have a dual role in cancer pathogenesis acting as an oncogene or as a tumor suppressor depending on the cancer type. We recently demonstrated that proteasomal degradation of EZH2 resulting from cyclin-dependent kinase 1 (CDK1)-induced phosphorylation at Threonine (T) 487 represents a novel mechanism of drug resistance in acute myeloid leukemia (AML). Our findings suggest that restoration of EZH2 protein is a viable approach to overcome therapy resistance in AML.

Keywords: Acute myeloid leukemia (AML); EZH2; drug resistance; epigenetic; proteasome.